Cyclocarya paliurus Triterpenoids Improve Diabetes-Induced Hepatic Inflammation via the Rho-Kinase-Dependent Pathway.

Cuihua Jiang,Nan Yao,Jian Zhang,Dongjian Zhang,Shiping Ma,Meng Gao,Qiaomei Jin,Yiting Wang,Zhiqi Yin

doi:10.3389/fphar.2019.00811

Abstract

This study aimed to assess the effects of triterpene extract of Cyclocarya paliurus (Batal.) Iljinskaja (CPT) on diabetes-induced hepatic inflammation and to unveil the underlying mechanisms. Diabetes in db/db mice was alleviated after CPT administration, as assessed by the oral glucose tolerance test. In addition, treatment with CPT dramatically reduced serum insulin, aspartate amino-transaminase, alanine aminotransferase, triglyceride, and total cholesterol amounts. Besides, serum levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were also reduced after CPT administration. Western blot analysis revealed that CPT treatment significantly reversed the protein expression levels of Rho, ROCK1, ROCK2, p-P65, p-IκBα, p-IKKα, and p-IKKβ in liver samples obtained from db/db mice. Upon palmitic acid stimulation, the protective effects of CPT on the liver were further assessed in HepG2 and LO2 cells, and no appreciable cytotoxic effects were found. Therefore, these findings indicate that CPT alleviates liver inflammation via Rho-kinase signaling. Chemical compounds evaluated in this report: Metformin (PubChem CID: 4091); Fasudil (PubChem CID: 3547); Palmitic acid (PubChem CID: 985).

Highlights

Diabetes mellitus (DM), a chronic ailment associated with metabolic disorders, features chronic hyperglycemia caused by insulin deficiency or resistance and is considered a serious global health burden (Makimattila et al, 1996; Abajobir et al, 2017)
Blood glucose levels in db/ db animals administered with Cyclocarya paliurus (Batal.) Iljinskaja (CPT) (0.25 or 0.5 g/kg) showed a significant increase at 30 min, but reversed to basal amounts within 2 h of glucose ingestion; a comparable trend was observed for the metformin and fasudil groups
Diabetes is mainly characterized by hyperglycemia, lack of insulin activity and insulin, and is one of the fastest growing health issues across the world

Summary

Introduction

Diabetes mellitus (DM), a chronic ailment associated with metabolic disorders, features chronic hyperglycemia caused by insulin deficiency or resistance and is considered a serious global health burden (Makimattila et al, 1996; Abajobir et al, 2017). Cyclocarya paliurus Diabetes-Induced Hepatic Inflammation multiple organs to elicit severe complications such as blindness, heart attack, gangrene, and liver cirrhosis, and these multiple abnormalities impose enormous clinical and economic burden on patients, families, and society (Harrison, 2006; Van Dieren et al, 2010; Seuring et al, 2015). Some antiinflammatory agents have important functions in increasing insulin sensitivity, ameliorating glucose control and attenuating live injury in several studies (Renata et al, 2006; Ford et al, 2015; MB et al, 2016). Therapeutic inhibition of hepatic inflammation may be potential strategies for DM and metabolic abnormalities (Saremi et al, 2010)

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